title: Extending the spectrum of Ellis van Creveld syndrome: a large family with a mild mutation in the EVC gene.
abstract: BACKGROUND
  Ellis-van Creveld (EvC) syndrome is characterized by short limbs, short ribs, postaxial polydactyly, dysplastic nails and teeth and is inherited in an autosomal recessive pattern. We report a family with complex septal cardiac defects, rhizomelic limb shortening, and polydactyly, without the typical lip, dental, and nail abnormalities of EvC. The phenotype was inherited in an autosomal recessive pattern, with one instance of pseudodominant inheritance.
  
  
  METHODS
  Because of the phenotypic overlap with EvC, microsatellite markers were used to test for linkage to the EVC/EVC2 locus. The results did not exclude linkage, so samples were sequenced for mutations.
  
  
  RESULTS
  We identified a c.1868T>C mutation in EVC, which predicts p.L623P, and was homozygous in affected individuals.
  
  
  CONCLUSIONS
  We conclude that this EVC mutation is hypomorphic and that such mutations can cause a phenotype of cardiac and limb defects that is less severe than typical EvC. EVC mutation analysis should be considered in patients with cardiac and limb malformations, even if they do not manifest typical EvC syndrome.
authors.affiliation: Genetic Disease Research Branch, National Human Genome Research Institute, NIH, Bethesda, MD, USA. ulucanh@mail.nih.gov
authors.forename: Hakan
authors.initials: H
authors.lastname: Ulucan
authors.forename: Davut
authors.initials: D
authors.lastname: Gül
authors.forename: Julie C
authors.initials: JC
authors.lastname: Sapp
authors.forename: John
authors.initials: J
authors.lastname: Cockerham
authors.forename: Jennifer J
authors.initials: JJ
authors.lastname: Johnston
authors.forename: Leslie G
authors.initials: LG
authors.lastname: Biesecker
mesh_terms: D000328:Adult; D000595:Amino Acid Sequence; D002648:Child; D004613:Ellis-Van Creveld Syndrome / Q000000981:diagnostic imaging / Q000235:genetics*; D005091:Exons; D005260:Female; D008040:Genetic Linkage; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D016350:Leucine Zippers / Q000235:genetics; D008297:Male; D008565:Membrane Proteins; D009154:Mutation; D010375:Pedigree; D010641:Phenotype; D011506:Proteins / Q000235:genetics*; D011859:Radiography; D016415:Sequence Alignment; D055815:Young Adult
chemical_list: C406058:EVC protein, human; C473310:EVC2 protein, human; D036341:Intercellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D011506:Proteins